- The cortical mantle is a highly specialized, folded structure composed of a thin layer of GM. Abnormal variations in the thickness of the cortical mantle might reflect pathophysiological changes of intrinsic structure and integrity of the cortical laminae. Recently, some studies have shown this correlation in chronic pain diseases such as back pain (Apkarian et al., 2004), migraine (DaSilva et al., 2007b; Granziera et al., 2006) and trigeminal neuropathic pain (see preliminary data). The implications of an alteration in these diseases are either degenerative processes or neuroplasticassociated mechanisms. Apkarian and colleagues (Apkarian et al., 2004) found reduction in the gray matter of DLPFC of chronic back pain patients when compared to healthy controls using a volumetric based approach. More recently, such GM volume reduction was also found in the parahippocampus, and cingulate cortex of patients with fibromyalgia when compared to healthy controls. However, it seems that similar changes observed in the GM of fibromyalgia patients may be more related to comorbid affective disorders than the pain endurance (Peres et al., 2004; Wood et al., 2009). Using more sensitive and reliable neuroimaging tools in trigeminal neuropathic pain patients our group found cortical thickness changes that were spatially co-localized with functional allodynic (brush induced pain) activation. In addition, this pattern of concurrent structural and functional changes in chronic pain patients is influenced by somatotopic localization (sensorimotor cortex), known functionality of the specific region (sensory-discriminative and affective-motivational), underline activation/deactivation following allodynic stimulation and the duration of the disorder (see preliminary data). In another study of migraine patients, we found increased cortical thickness of caudal sensorimotor cortex in migraineurs compared to controls (DaSilva et al., 2007a). In the cortical mantle, the thickness changes in the sensory cortex could be due to the chronic sensory stimulation provoked by chronic pain. This is in line with a recent study that showed cortical thickening after sustained stimulation of the motor system (Draganski et al., 2004). In this study, volunteers who have learned to juggle showed transient and selective thickening of the motor cortex, as well as the motion-visual areas (MT/V5), as compared to the pre-learned phase. This suggests that overstimulation of the sensory-discriminative and affective-motivational neuronal systems in chronic pain may induce structural alterations in the cortex that is co-localized with inefficient pain modulation by the opioidergic system at a molecular level.